The central involvement of the monoamines NA, DA, and 5-HT in the elaboration of or protection against audiogenic seizures in mice is being analyzed, particularly as a function of postnatal age. Three model systems are utilized and in all, seizures are most prominently manifest at a certain age: (1) DBA/BL/6 MICE--a strain with a genetically determined susceptibility to audiogenic seizures with the highest incidence of seizures apparent at 21 days. (2) Accoustically primed seizures. C57BL/6 mice are normally resistant to sound-induced seizures but when exposed to the sound stimulus at 16 days they elicit full seizures at 21 days. (3) Drug-induced audiogenic seizures. A drug with the structure of a catecholamide (H13/04) has been analyzed over the past year and it has been found to elicit maximal audiogenic seizures in resistant strains of mice at 21-28 days of age. Pharmacologically, sound-induced audiogenic seizures in all models can be prevented by pretreatment with clonidine, a NA-receptor-stimulating agent, as well as by L-DOPA AND 5-HTP. Additionally the acoustically-primed seizure can be prevented if the animals are given clonidine before priming. Hence, activation of NA receptors activated by clonidine is not yet understood. A deficient development of NA receptors in the genetically sensitive mice could be expected to result in enhanced rates of synthesis or turnover of the transmitter via feedback. However, an enhanced synthesis of NA was observed in the sensitive strain only at 14 days of age as compared to the resistant strain. Changes in transmitter chemistry may not necessarily parallel in age the maximal elaboration of the seizure, particularly in a strain with a genetically-determined susceptibility. The turnover of the monoamines and the uptake and use of radiolabelled monoamine precursors during presentation of the sound stimulus are also being analyzed. With an understanding of mechanisms responsible for the elaboration of audiogenic seizures, will hopefully come an understanding of their prevention and management.